Balloon for treatment of stenosis and method for manufacturing the balloon

ABSTRACT

The present invention relates to a balloon ( 1 ) for treating stenosis and the method for obtaining this balloon. The method comprises the steps of: bringing the balloon in the deployed configuration; placing a plurality of stylets ( 17 ) that are arranged in the axial direction along the outer wall ( 10 ) of the balloon, pushing the stylets towards the balloon core ( 11 ) in the radial direction such as to form a plurality of laps ( 12 ); laying the laps about the core in the tangential direction such as to lay each lap on an adjacent stylet; removing the stylets such as to form a plurality of cavities ( 13 ) comprised between each lap and the balloon core; filling the cavities with the drug.

The present invention relates to a balloon and a catheter forangioplasty and pharmacologic treatment of stenosis. The inventionfurther relates to a method for manufacturing the balloon and catheter.

Catheters for the angioplasty treatment of stenosis within the humanbody circulatory system have been known for a long time. These catheterscomprise a balloon at the distal end thereof. The balloon is insertedwithin the blood vessels in a deflated configuration and is broughtproximate to the stenosis, where it is inflated. Thereby, a mechanicaltreatment of the stenosis is obtained, which is suitable to restore thesection of the blood vessel.

It has been recently noted that the effectiveness of this merelymechanical angioplasty operation results to be dramatically improvedwhen a drug suitable to prevent restenosis is used in associationtherewith. Suitable drugs for this kind of treatment are anti-tumourdrugs that are adapted to be used as antiproliferatives. These drugs canbe, for example: Rapamycin, Epothilone, and mainly Paclitaxel.

Particularly, attempts have been made to coat the angioplasty balloonwith a gelatinous layer consisting of a mixture of a suitable solventand Paclitaxel. In the previous patent applications: WO 2004/028610, WO2004/028582, and WO 2002/076509, of which the appointed inventor isProfessor Ulrich Speck, has been described how a lipophilic drug, suchas Paclitaxel, can be positioned on the outer portion of an angioplastyballoon.

This known method, however, is not without defects.

First of all, in order to reach the length that presents the stenosis,the balloon is required to travel along a relatively long pathway withinthe healthy blood vessels. Along this pathway, the drug is very likelyto be partially removed due to friction against the healthy vesselwalls.

This determines some undesirable consequences. First, it determines theadministration of an amount of drug near the stenosis which is lowerthan expected and a priori unknown. Secondly, it determines thedispersion of a powerful drug in healthy districts of the body, withconsequent undesirable secondary effects. Thirdly, it has been notedthat after the drug has been carried proximate to the stenosis, this canbe immediately dispersed immediately after normal blood flow has beenrestored.

The object of the present invention is to provide an angioplastyballoon, the catheter thereof and the method for manufacturing the same,which allow at least partially overcoming the drawbacks mentioned abovewith reference to the prior art.

More particularly, the task of the present invention is to provide anangioplasty balloon which allows administering all the drug providedthereon in the stenosis area upon being introduced within the patient'sbody.

A further task of the present invention is to provide an angioplastyballoon, which restrains the dispersion of the drug in healthy districtsof the patient's body.

The task of the present invention is further to provide an angioplastydevice which restrains the dispersion of the drug after it has beenreleased, thereby preventing the washing effect that commonly occurswhen the normal blood flow has been restored.

This object and these tasks are achieved by an angioplasty balloon inaccordance with claim 1, a catheter in accordance with claim 23 and amethod for manufacturing the balloon in accordance with claim 25.

Further features and advantages of the present invention will be betterunderstood from the description of some exemplary embodiments, which isgiven below by way of non-limiting illustration, with reference to thefollowing figures:

FIG. 1 is a side view of an angioplasty catheter of the prior art;

FIG. 2 is the section along the line II-II in FIG. 1;

FIG. 3 a is a possible section along the line III-III in FIG. 1;

FIG. 3 b is another possible section along the line III-III in FIG. 1;

FIG. 4 a to 4 d are front views of an angioplasty balloon duringsubsequent steps of the method according to the invention;

FIG. 5 is a partially sectional side view of an angioplasty balloonduring a step of a method according to the invention;

FIG. 6 a to 6 d are different possible sections of the stylet shown inFIG. 5;

FIG. 7 is a perspective view of the balloon according to the inventionin a collapsed configuration;

FIG. 8 is a perspective view of the balloon according to the inventionin a deployed configuration;

FIG. 9 is a side view of a balloon according to the invention in adeployed configuration;

FIG. 10 a is a side view of a balloon according to the invention in asemi-deployed configuration;

FIG. 10 b shows the balloon in FIG. 10 a in a deployed configuration;

FIG. 11 is a side view of a balloon according to the invention in adeployed configuration;

FIG. 12 a is a side view of a balloon according to the invention in acollapsed configuration;

FIG. 12 b shows the balloon in FIG. 12 a in a semi-deployedconfiguration.

With reference to the figures, with 1 has been designated an angioplastyballoon that is mounted at the distal end of a catheter 2.

The catheter 2 further comprises, in a manner known per se, an elongatedtubular body 3 that is provided with a plurality of lumens 4, and of aconnector 5 at the proximal end thereof.

The balloon 1, in a manner known per se, is suitable to alternativelyadopt a deployed configuration and a collapsed configuration. Theballoon is brought to the deployed configuration by means of theinjection of a pressurized inflating liquid, and vice versa, is broughtto the collapsed configuration by means of the suction of the inflatingliquid.

The balloon is suitable, in the collapsed configuration, to be insertedwithin the circulatory system of a patient's body and to be advancedalong the vessels to reach a vessel section that is affected bystenosis. The balloon 1 is further suitable to apply, when it passesfrom the collapsed configuration to the deployed configuration, a radialforce to the stenosis such as to expand the latter and restore thenominal section of the vessel.

The balloon 1 comprises an outer wall 10 and a core 11 matching with thedistal end of the catheter 2. The core 11 defines an axis X about whichthe balloon 1 is developed.

By the term “axial” below is meant the direction of a straight lineparallel to the axis X. By the term “radial” below is meant thedirection of a half-line originating on the axis X and perpendicularthereto. Finally, by the term “circumferential” (or “tangential”) ismeant below the direction of a circumference (or tangent thereof) thatis centered on the axis X and lying on a plane perpendicular to the axisX.

In the collapsed configuration, the balloon 1 according to the invention(see FIGS. 4 d and 7) comprises a plurality of laps 12 that are laidabout the core 11 in the circumferential direction. Each of the laps 12is laid such as to provide a cavity 13 comprised between the lap and thecore 11. The cavities 13 are filled with a drug 14.

In the deployed configuration, the balloon 1 according to the invention(see FIG. 8) comprises a plurality of bands 15 of drug 14 that areaxially arranged along the outer wall 10. The bands 15 of drug 14 arealternated in the circumferential direction with strips 16 in which thedrug 14 is not provided and the outer wall 10 is directly exposed.

The number of bands 15, and consequently the number of strips 16, arelinked to the number of laps 12. For example, the presence of three laps12 when the balloon is in the collapsed configuration, determines thepresence of three bands 15 of drug 14 that are alternated with as manycleaned strips 16.

In accordance with an embodiment, the bands 15 of drug 14 are wide abouttwice the strips 16.

The bands 15 are preferably equally spaced relative to each other in acircumferential direction along the outer wall 10 of the balloon 1.

In accordance with an embodiment of the invention, the balloon 1comprises three laps 12. In accordance with other possible embodiments,the laps 12 can be provided in a different number in order to meetparticular requirements.

In accordance with an embodiment of the balloon, the drug 14 comprisesthe Paclitaxel as the active ingredient. The Paclitaxel is availablewith the trade name of Taxol®, which is a registered mark ofBristol-Myers Squibb.

In accordance with other embodiments, the drug 14 comprises otheranti-tumour active ingredients that are suitable to be employed asantiproliferatives, such as: Rapamycin or Epothilone.

In accordance with an embodiment, the drug 14 comprises the activeingredient and a suitable excipient, for example a gel or a paste beingsuitable to penetrate within the cavities 13 and adhere to the wall 10of the balloon 1.

In accordance with several possible embodiments of the invention, theballoon 1 according to the invention comprises containment means 20 tobe capable of stopping the blood flow in the length in which theangioplasty operation has to be carried out.

The containment means 20 allow avoiding the washing effect in the bloodflow which tends to remove and disperse the drug 14 immediately afterthe application by means of the balloon 1. In other words, as the bloodflow is temporary stopped, the lipophilic drug can take the timerequired for linkage to the vessel walls. A dramatically lower washingeffect occurs during the subsequent restoration of the flow.

In accordance with the embodiment depicted in FIG. 9, the containmentmeans 20 comprise two auxiliary balloons 21 that are located atimmediately proximal and immediately distal positions relative to theballoon 1.

In accordance with the embodiment depicted in FIG. 11, the containmentmeans 20 comprise an individual auxiliary balloon 21 which is located atan immediately distal position relative to the balloon 1.

The auxiliary balloons 21 are suitable to pass from a collapsedconfiguration, in which they have minimum radial overall dimensions, toan deployed configuration (illustrated in FIGS. 9 and 11) in which theyare suitable to come in contact with the walls of the blood vessel suchas to stop the flow.

In accordance with an embodiment, the auxiliary balloons 21 aredifferent from the balloon 1 in that they consist of an elastic wall andare not suitable to apply the radial force that is required for theangioplasty operation.

In accordance with an embodiment, the catheter 2 comprises aninflation/deflation duct for the balloon 1 and an individualinflation/deflation duct for the auxiliary balloons 21, even when two ofthem are provided. In accordance with another embodiment, the catheter 2comprises an inflation/deflation duct for the balloon 1 and aninflation/deflation duct for each of the auxiliary balloons 21.

In the description of the procedure for using the catheters of FIGS. 9and 11, reference is made to the auxiliary balloons 21, obviouslyconsidering also the case in which only one auxiliary balloon 21 isprovided. The procedure for using the balloon 1 provides:

inserting the catheter 2 within the site to be treated;

bringing the auxiliary balloons 21 from the collapsed configuration tothe deployed configuration;

bringing the balloon 1 from the collapsed configuration to the deployedconfiguration such as to carry out the angioplasty operation and thedeposition of the drug on the vessel walls;

bringing the balloon 1 from the deployed configuration to the collapsedconfiguration;

after a reasonable time (for example a few seconds), bringing theauxiliary balloons 21 from the deployed configuration to the collapsedconfiguration;

removing the catheter.

In accordance with the embodiment as depicted in FIGS. 10 a and 10 b,the containment means 20 comprises two shaped portions 22 of the balloon1. The shaped portions 22 are obtained as one piece with the balloon 1and are placed at the ends, respectively distal and proximal, of theballoon 1.

The balloon 1 in FIG. 10 is capable of adopting three configurations:

a collapsed configuration (non illustrated), in which it has minimumradial overall dimensions;

a deployed configuration (FIG. 10 a), in which it has maximum radialoverall dimensions, and is capable of applying a radial force that issufficient to bring the angioplasty operation to completion;

a semi-deployed configuration (FIG. 10 b) wherein the shaped portions 22maintain the maximum radial overall dimensions, whereas the centrallength of the balloon adopt intermediate radial overall dimensions.

In accordance with the embodiment, the deployed configuration of theballoon 1 is obtained by means of a first level of internal pressure,whereas the semi-deployed configuration is obtained with a second levelof internal pressure. The first level of pressure can be for exampleequal to about 14 bars, whereas the second level of pressure can be forexample equal to about 7 bars.

The procedure for using the balloon 1 in FIG. 10 provides:

inserting the catheter 2 within the site to be treated;

bringing the balloon 1 from the collapsed configuration to the deployedconfiguration such as to carry out the angioplasty operation and thedeposition of the drug on the vessel walls;

bringing the balloon 1 from the deployed configuration to thesemi-deployed configuration;

after a reasonable time (for example a few seconds), bringing theballoons 1 from the semi-deployed configuration to the collapsedconfiguration;

removing the catheter 2.

In accordance with the embodiment in FIG. 10, the catheter 2 comprisesan individual inflation/deflation lumen for the balloon 1 and shapedportions 22.

In accordance with an embodiment of the invention, an angioplasty stent6 is also fitted on the balloon 1. The stent 6, in a manner known perse, has a tubular structure that can alternatively adopt a collapsedconfiguration and a deployed configuration, similarly as the balloon 1.

FIG. 12 a schematically illustrates a balloon 1 according to theinvention comprising a stent 6. The balloon 1 and the stent 6 are bothin a collapsed configuration, and the stent 6 is either fitted or firmlywrapped onto the balloon 1. In this configuration, the stent 6 iscapable of maintaining the laps 12 in position, such that they are notlifted and the drug 14 does not escape from the cavities 13.

The provision of the stent 6, in addition to meeting particulartherapeutic requirements, can result particularly advantageous also whenthe pathway within the patient's blood vessels is particularly tortuous.In fact, when the balloon 1 is required to perform a curve with a smallcurvature radius (for example in the order of half the length of theballoon or less) the curvature imposed to the balloon 1 can cause one ormore laps 12 to be lifted. The provision of the stent 6, on thecontrary, avoids this risk, by setting a radial constraint upon the laps12.

Furthermore, the presence of the stent 6 varies the inflating mode ofthe balloon 1, i.e., the presence of the stent 6 influences the mode inwhich the balloon 1 moves from the collapsed configuration to thedeployed configuration. In fact, during the inflation of the balloon 1without stent 6, the diameter of the balloon increases in a quite evenmanner along the axis X. The balloon 1 passes from the collapsedconfiguration (see for example FIG. 7) to the deployed configuration(see for example FIG. 8) while maintaining a substantially rectilinearprofile of the central part of wall 10.

When the balloon 1 that is wrapped within the stent 6 is being inflated,the diameter of the balloon increases, this time in an uneven manner,along the axis X. At the ends of the balloon 1, the radial resistance ofthe stent 6 is more easily overcome by the pressure applied within theballoon 1. Due to this fact, in a semi-deployed configuration, theassembly consisting of the balloon 1 and stent 6 temporarily adopts theshape as outlined in FIG. 12 b. As my be noted, in this semi-deployedconfiguration, the central length of the wall 10 of balloon 1 is curved,thereby maintaining lower diameter values in the central sections andtaking increasingly greater diameter values as moving to the endsections. Thereby, the distal and proximal ends of the balloon 1 act asthe containment means 20 described above, which are suitable totemporary stop the blood flow in the length involved in the angioplastyoperation.

According to a further aspect, the invention relates to a catheter 2 forangioplasty comprising at least one balloon 1 described above.

The method according to the invention for depositing the drug on theballoon 1 as described above, comprises the following steps:

arranging the balloon 1 in a collapsed configuration;

placing a plurality of stylets 17 being arranged in an axial directionbetween each lap 12 and the core 11 of the balloon 1;

pressing the laps 12 in the radial direction on the core 11 such as tomatch each lap 12 with the underlying stylet 17;

removing the stylets 17 such as to form a plurality of cavities 13 thatare comprised between each lap 12 and the core 11 of the balloon 1;

filling the cavities 13 with a drug 14.

In accordance with a particular embodiment, the step described above ofplacing the stylets 17 between each lap 12 and core 11 of the balloon 1,comprises the following steps:

injecting the inflating liquid into the balloon 1 such as to bring thelatter in the deployed configuration;

placing a plurality of stylets 17 being arranged in the axial directionalong the outer wall 10 of the balloon 1;

pushing the stylets 17 in the radial direction towards the core 11 ofthe balloon 1 such as to form a plurality of laps 12;

laying the laps 12 in the tangential direction about the core 11 such asto lay each lap 11 on a stylet 17 adjacent thereto;

sucking the inflation liquid from the balloon 1 such as to bring it backto the collapsed configuration thereof.

In accordance with different embodiments of the method, the stylets 17can have different sections according to the particular requirements. InFIG. 6 a to 6 d, several possible sections of the stylets 17 areillustrated by way of example.

In accordance with an embodiment of the method, the drug 14 is drippedwithin the cavities 13 that have formed when the stylets 17 have beenremoved.

In accordance with several embodiments of the method, the stylets arehollow and are suitable to deliver the drug 14 that is intended to fillthe cavities 13. Preferably, during the step of removing the stylets 17,from the end of each stylet 17 a volume of drug 14 is delivered, whichis suitable to fill the cavity 13 that will be formed as the stylet isbeing removed.

In accordance with these embodiments of the method, the stylets 17 havethus a hollow section, unlike what has been illustrated in FIG. 6 a to 6d.

In accordance with several embodiments of the method, the drug 14 issucked within the cavity 13 by applying a suitable depressurization.

In accordance with several embodiments of the method, the drug 14 isarranged at an end of the cavities 13 (such as at the distal end) and isthen sucked within the cavities 13 by applying a depressurization at theopposite end (such as at the proximal end).

In any case, the amount of drug 14 being arranged within the cavities 13has to be adjusted such as to ensure that the proper amount of activeingredient is brought in contact with the vessel wall during theangioplasty operation.

In accordance with several embodiments of the method (see for exampleFIGS. 4 d and 5), during the step of filling the cavities 13 with thedrug 14, the balloon 1 is wrapped within a protective sheath 18. Theprotective sheath 18 has the purpose of keeping the laps 12 in position,such that the drug 14 does not escape from the cavities 13.

From what has been set forth above, those skilled in the art mayappreciate how the balloon according to the invention can at leastpartially overcome the drawbacks of prior art balloons.

In fact, in the balloon according to the invention, when in thecollapsed configuration, the drug 14 is protected by the laps 12. Inother words, when the balloon 1 is in the collapsed configuration, thedrug 14 is not exposed to contact with the external environment, andonly the strips 16 of the wall not covered with drug 14 are exposed.This characteristic allows the balloon to be advanced along the vesselsof the circulatory system without dispersing the drug intended for thestenosis in healthy districts along the pathway.

It is understood that only some particular embodiments of the balloonand method for manufacturing the same according to the present inventionhave been described, to which the man skilled in the art shall be ableto bring any modifications required to adapt it to particularapplications, without however departing from the scope of protection asdefined in the claims below.

1. A balloon for angioplasty suitable to adopt a deployed configurationand a collapsed configuration, having an outer wall and a core definingan axis, the balloon comprising in the collapsed configuration aplurality of laps that are laid in a tangential direction about the coreof the balloon such as to form a plurality of cavities, wherein thecavities are filled with a drug.
 2. The balloon according to claim 1wherein, in the collapsed configuration, the balloon is suitable to beinserted within the circulatory system of a patient's body and to beadvanced along the vessels to reach a vessel section that is affected bystenosis.
 3. The balloon according to any preceding claim 1 wherein,when the balloon passes from the collapsed configuration to the deployedconfiguration, it is suitable to apply a radial force to a stenosis suchas to expand the latter and restore the nominal section of the patient'sblood vessel.
 4. The balloon according to any preceding claim 1 wherein,in the deployed configuration, the balloon comprises a plurality ofbands of drug that are axially arranged along the outer wall.
 5. Theballoon according to the preceding claim 1 wherein the bands of drug arealternated in the circumferential direction with strips in which thedrug is not provided, and the outer wall is directly exposed.
 6. Theballoon according to claim 4 wherein the bands of drug are about twicewider than the strips.
 7. The balloon according to 6 claim 4 wherein thebands are equally spaced from each other in the circumferentialdirection along the outer wall of the balloon.
 8. The balloon accordingto claim 5 wherein, when the balloon is in the collapsed configuration,the drug is protected by the laps i.e. the drug is not exposed tocontact with the external environment and only the strips of wall thatis not covered with drug are exposed.
 9. The balloon according to claim1 wherein the drug is lipophilic.
 10. The balloon according to claim 1wherein the drug comprises an anti-tumour active ingredient suitable tobe employed as an antiproliferative and a suitable excipient.
 11. Theballoon according to claim 1 wherein the drug contains Rapamycin,Epothilone or preferably Paclitaxel as the active ingredient.
 12. Theballoon according to claim 9 wherein the excipient is a gel or pastesuitable to penetrate within the cavities and adhere to the wall of theballoon.
 13. The balloon according to claim 1 further comprisingcontainment means to be capable of stopping the blood flow in the lengthwhere the angioplasty operation has to be carried out.
 14. The balloonaccording to claim 13 wherein the containment means are capable ofavoiding the washing effect in the blood flow, which tends to remove anddisperse the drug immediately after the application by means of theballoon.
 15. The balloon according to claim 13 wherein the containmentmeans comprise an auxiliary balloon that is placed in an immediatelydistal position relative to the balloon.
 16. The balloon according toclaim 13 wherein the containment means comprise two auxiliary balloonsthat are placed in immediately proximal and immediately distal positionsrelative to the balloon.
 17. The balloon according to claim 15 whereinthe auxiliary balloons are suitable to pass from a collapsedconfiguration with minimum radial overall dimensions, to a deployedconfiguration in which they are suitable to come in contact with thewalls of a blood vessel such as to stop the blood flow.
 18. The balloonaccording to claim 15 wherein the auxiliary balloons are not suitable toapply the radial force that is required for the angioplasty operation.19. The balloon according to claim 13 wherein the containment meanscomprise two shaped portions of the balloon.
 20. The balloon accordingto claim 19, wherein the shaped portions are obtained as one piece withthe balloon and are connected to the ends, distal and proximal of theballoon, respectively.
 21. The balloon according to claim 19 wherein theballoon is capable of adopting: a collapsed configuration with minimumradial overall dimensions; a deployed configuration in which it hasmaximum overall dimensions and is suitable to apply a radial forcesufficient to bring the angioplasty operation to completion; asemi-deployed configuration, in which the shaped portions maintain themaximum radial overall dimensions, whereas the central length of theballoon adopts intermediate radial overall dimensions.
 22. The balloonaccording to claim 1 further comprising a stent being fitted on theballoon.
 23. A catheter for angioplasty comprising a balloon forangioplasty suitable to adapt a deployed configuration and a collapsedconfiguration, said balloon having an outer wall and a core defining anaxis, the balloon comprising in the collapsed configuration a pluralityof laps that are laid in a tangential direction about the core of theballoon so as to form a plurality of cavities, wherein the cavities arefilled with a drug.
 24. The catheter according to claim 23 wherein theballoon is mounted to the distal end of the catheter. 25-32. (canceled)